The present invention relates to novel compounds which are 2-substituted .alpha.-benzylidene-.gamma.-butyrolactone, .alpha.-benzylidene- .delta.-valerolactone .alpha.-benzylidene-.gamma.-butyrolactam, and .alpha.-benzylidene-.delta.-valerolactam derivatives of the fenamic acids. The invention compounds have activity as inhibitors of the IL-1-induced proteoglycan (PG) degradation in bovine nasal cartilage providing treatment of conditions advantageously affected by such inhibition including arthritis, and the like. IL-1 is one example of an agonist causing PG degradation. Other agonists including TNF and PMA also cause PG degradation. The compounds of the present invention block PG degradation caused by various agonists, and the description of inhibit ion of IL-1 induced PG degradation is illustrative rather than exclusive.
Although fenamates are known antiinflammatory agents and various substituted .alpha.-benzylidene-.gamma.-butyrolactone and .alpha.-benzylidene-.gamma.-butyrolactam derivatives are known as useful substituents in derivations of 3,5-di-tertiary-butyl-4-hydroxyphenyl groups as disclosed in U.S. Pat. No. 4,431,656 and in European Patent Publication 0204964, the present combination of ring systems, substituents, and moieties is not among those previously known.